Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response

Luisa Matos do Canto, Sarah Santiloni Cury, Mateus Camargo Barros-Filho, Bruna Elisa Catin Kupper, Maria Dirlei Ferreira de Souza Begnami, Cristovam Scapulatempo-Neto, Robson Francisco Carvalho, Fabio Albuquerque Marchi, Dorte Aalund Olsen, Jonna Skov Madsen, Birgitte Mayland Havelund, Samuel Aguiar, Silvia Regina Rogatto*

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Resumé

Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.

OriginalsprogEngelsk
Artikelnummer8702
TidsskriftScientific Reports
Vol/bind9
Antal sider11
ISSN2045-2322
DOI
StatusUdgivet - 18. jun. 2019

Fingeraftryk

Rectal Neoplasms
Neoplasms
Proteins
Proteome
Computer Simulation
Databases
Serum

Citer dette

Canto, Luisa Matos do ; Cury, Sarah Santiloni ; Barros-Filho, Mateus Camargo ; Kupper, Bruna Elisa Catin ; Begnami, Maria Dirlei Ferreira de Souza ; Scapulatempo-Neto, Cristovam ; Carvalho, Robson Francisco ; Marchi, Fabio Albuquerque ; Olsen, Dorte Aalund ; Madsen, Jonna Skov ; Havelund, Birgitte Mayland ; Aguiar, Samuel ; Rogatto, Silvia Regina. / Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response. I: Scientific Reports. 2019 ; Bind 9.
@article{7613fe711a7942fa9850f79e6d37e25d,
title = "Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response",
abstract = "Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.",
author = "Canto, {Luisa Matos do} and Cury, {Sarah Santiloni} and Barros-Filho, {Mateus Camargo} and Kupper, {Bruna Elisa Catin} and Begnami, {Maria Dirlei Ferreira de Souza} and Cristovam Scapulatempo-Neto and Carvalho, {Robson Francisco} and Marchi, {Fabio Albuquerque} and Olsen, {Dorte Aalund} and Madsen, {Jonna Skov} and Havelund, {Birgitte Mayland} and Samuel Aguiar and Rogatto, {Silvia Regina}",
year = "2019",
month = "6",
day = "18",
doi = "10.1038/s41598-019-45151-w",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

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Canto, LMD, Cury, SS, Barros-Filho, MC, Kupper, BEC, Begnami, MDFDS, Scapulatempo-Neto, C, Carvalho, RF, Marchi, FA, Olsen, DA, Madsen, JS, Havelund, BM, Aguiar, S & Rogatto, SR 2019, 'Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response', Scientific Reports, bind 9, 8702. https://doi.org/10.1038/s41598-019-45151-w

Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response. / Canto, Luisa Matos do; Cury, Sarah Santiloni; Barros-Filho, Mateus Camargo; Kupper, Bruna Elisa Catin; Begnami, Maria Dirlei Ferreira de Souza; Scapulatempo-Neto, Cristovam; Carvalho, Robson Francisco; Marchi, Fabio Albuquerque; Olsen, Dorte Aalund; Madsen, Jonna Skov; Havelund, Birgitte Mayland; Aguiar, Samuel; Rogatto, Silvia Regina.

I: Scientific Reports, Bind 9, 8702, 18.06.2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response

AU - Canto, Luisa Matos do

AU - Cury, Sarah Santiloni

AU - Barros-Filho, Mateus Camargo

AU - Kupper, Bruna Elisa Catin

AU - Begnami, Maria Dirlei Ferreira de Souza

AU - Scapulatempo-Neto, Cristovam

AU - Carvalho, Robson Francisco

AU - Marchi, Fabio Albuquerque

AU - Olsen, Dorte Aalund

AU - Madsen, Jonna Skov

AU - Havelund, Birgitte Mayland

AU - Aguiar, Samuel

AU - Rogatto, Silvia Regina

PY - 2019/6/18

Y1 - 2019/6/18

N2 - Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.

AB - Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.

U2 - 10.1038/s41598-019-45151-w

DO - 10.1038/s41598-019-45151-w

M3 - Journal article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 8702

ER -